Microcephaly

Gene: COPB2

I don't know

PMID: 37734708 - This paper reports an unrelated individual with the same homozygous variant (NM_004766.3:c.760C>T, p.Arg254Cys) identified in 2xsiblings in PMID: 29036432 (the same two siblings are also described in PMID: 34450031).

The proband is an 8.5yo Iranian female born to consanguineous parents. This individual has symptoms consistent with autosomal recessive microcephaly 19 (MIM#617800) including, global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms; she is unable to stand, walk, or speak.

Created: 27 Dec 2023, 6:08 a.m. | Last Modified: 27 Dec 2023, 6:09 a.m.

Panel Version: 1.246

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly 19, primary, autosomal recessive, MIM# 617800

Publications

• 37734708
• 29036432
• 34450031

I don't know

Loss-of-function variants in COPB2, a component of the COPI coatomer complex, in six individuals from five unrelated families. 4 are heterozygous and one family with two sibs with homozygous variant, previously reported.
All presenting with a clinical spectrum of osteoporosis or osteopaenia, many with recurrent fractures, and developmental delay of variable severity. Functional data.

Note one of the individuals with heterozygous variant had significant microcephaly in addition to the two sibs with bi-allelic variants.

Created: 13 Sep 2021, 7:55 a.m. | Last Modified: 13 Sep 2021, 7:55 a.m.

Panel Version: 1.45

Two sibs with homozygous missense variant in this gene, mice homozygous for this variant had normal brain size however. Mice compound het for null allele and missense variant had some brain features, suggesting the missense variant is hypomorphic.
Sources: Expert list

Created: 2 Apr 2021, 6:31 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Microcephaly 19, primary, autosomal recessive, MIM# 617800

Publications

• 29036432
• 34450031